Faculty Affairs and Academic Programs
Jonathan David Herman MD PhD
Medical; Health Sciences; Nursing
Developing Antigen-Specific B-cell Receptor Repertoires to the Whole Malaria Proteome to Inform Vaccine Development
In 2023, there were more than 263 million cases of malaria world-wide and return of local transmission of malaria in the United States after a 2-decade hiatus. Though we have two WHO pre-qualified malaria vaccines, we still need a highly effective, long lasting malaria vaccine and will likely need to identify novel protective targets to achieve this. B cells, the immune cells that make and secrete antibodies, are crucial parts of the protective immune response to malaria and malaria vaccines. B-cell receptor (BCR) repertoires, i.e. measuring and categorizing the sequence of all the B-cell receptors in a person, have great hope to help us diagnose disease and design better vaccines however current methods can only determine the target of these B cells to up to 10 antigens at a time. We have already developed Plasmoscan, a malaria phage display immunoprecipitation assay (PhIP-Seq) that enables us to measure antibody responses to the entire malaria proteome. We will use our expertise in systems antibody immunology and PhIP-Seq to develop a novel technology to measure the antigen specificity of a BCR to the entire malaria proteome (Aim 1) and harness this breakthrough technology to identify novel protective epitopes from individuals vaccinated with the live cell malaria vaccine PfSPZ. Overall, we will identify novel protective epitopes that will inform second-generation malaria vaccine development and develop a field-changing Ag-specific BCR sequencing methodology that will revolutionize how we study adaptive immunity in humans and develop vaccines and monoclonal antibody therapeutics.
